Biology subjects

Kauffmann, L.

Publications and source records attributed to Kauffmann, L..

3 recordsLinked to original sources

bioRxiv2026

Lipid Droplet Targeting Drives Substrate Access during Very Long Chain Fatty Acid Activation by Fat1

Fatty acids, the most abundant building blocks for lipid synthesis, require conjugation with Coenzyme A (CoA) for their incorporation into membrane lipids. Of those, very long chain fatty acids (VLCFAs), the precursors of yeast ceramides, are particularly hydrophobic. Yet it remains unresolved where and how the sole VLCFA-CoA synthetase Fat1 activates them. Here we show that lipid droplets (LDs) are both the site of free VLCFAs storage, as well as their place of activation. Free VLCFAs preferentially partition into LDs in molecular simulations and in vitro reconstitutions, whereas Fat1 targets the LD surface in cells via a N-terminal amphipathic helix. Structural predictions identify an essential hydrophobic cavity in Fat1 that connects the active site to the membrane, suggesting that VLCFAs directly shuttle from the LD core into the enzymatic pocket. Our model explains how the organelle targeting of a fatty acid activator evolved to match the biophysical properties and consequently the subcellular localization of its highly hydrophobic substrate.

biochemistry↗

bioRxiv2022

Dysfunction of the visual sensory thalamus in developmental dyslexia

Developmental dyslexia (DD) is a reading disorder with a prevalence of 5-10%. Neuroscientific research has typically focused on explaining DD symptoms based on pathophysiological changes in the cerebral cortex. However, DD might also be associated with alterations in sensory thalami - central subcortical stations of sensory pathways. A post-mortem study on the visual sensory thalamus (lateral geniculate nucleus, LGN) showed histopathological changes in the magnocellular (M-LGN), but not in the parvocellular (P-LGN), subdivisions. M-LGN and P-LGN have different functional properties and belong to two different visual systems. Whether M-LGN alterations also exist in DD in-vivo is unclear. Also, the potential relevance of M-LGN alterations to DD symptoms is unknown. This lack of knowledge is partly due to considerable technical challenges in investigating LGN subdivisions non-invasively in humans. Here, we employed recent advances in high-field 7 Tesla functional magnetic resonance imaging (fMRI) to map the M- and P-LGN in-vivo in DD adults (n=26) and matched controls (n=28). We show that (i) M-LGN responses differ between DD and control participants, (ii) these differences are more pronounced in male than in female DD participants, and (iii) M-LGN alterations predict a core symptom of DD in male DD participants only, i.e., rapid naming ability. Our results provide a first functional interpretation of M-LGN changes in DD and support DD theories that propose a direct relevance of sensory thalamus alterations for DD symptoms. In addition, the sex-specific behavioral relevance of M-LGN alterations within DD calls for taking sex differences into account when planning brain-based therapeutic interventions. Significance StatementDevelopmental dyslexia (DD) is one of the most common learning disorders affecting millions of children and adults world-wide. Several decades ago, pioneering research in five DD post-mortem brains suggested that DD is characterized not only by alterations of the cerebral cortex, but also by changes in a subsection of the visual sensory thalamus - the so-called M-LGN. The relevance of these findings for DD remained highly controversial. Using recent developments in high-resolution functional neuroimaging, we now discovered that M-LGN alterations are present also in DD in-vivo and predict a core symptom of DD in males. Our results provide a first functional interpretation of M-LGN alterations in DD and provide a basis for better understanding sex-specific differences in DD.

neuroscience↗

bioRxiv2020

Mapping the Human Visual Thalamus and its Cytoarchitectonic Subdivisions Using Quantitative MRI

The human lateral geniculate nucleus (LGN) of the visual thalamus is a key subcortical processing site for visual information analysis. A non-invasive assessment of the LGN and its functionally and microstructurally distinct magnocellular (M) and parvocellular (P) subdivisions in-vivo in humans is challenging, because of its small size and location deep inside the brain. Here we tested whether recent advances in high-field structural quantitative MRI (qMRI) can enable MR-based mapping of human LGN subdivisions. We employed ultra-high resolution 7 Tesla qMRI of a post-mortem human LGN specimen and high-resolution 7 Tesla in-vivo qMRI in a large participant sample. We found that a quantitative assessment of the LGN and a differentiation of its subdivisions was possible based on microstructure-informed MR-contrast alone. In both the post-mortem and in-vivo qMRI data, we identified two components of shorter and longer longitudinal relaxation time (T1) within the LGN that coincided with the known anatomical locations of a dorsal P and a ventral M subdivision, respectively. Through a subsequent ground truth histological examination of the same post-mortem LGN specimen, we showed that the observed T1 contrast pertains to cyto- and myeloarchitectonic differences between LGN subdivisions. These differences were based on cell and myelin density, but not on iron content. Our qMRI-based mapping strategy overcomes shortcomings of previous fMRI-based mapping approaches. It paves the way for an in-depth understanding of the function and microstructure of the LGN in humans. It also enables investigations into the selective contributions of LGN subdivisions to human behavior in health and disease. Significance StatementThe lateral geniculate nucleus (LGN) is a key processing site for the analysis of visual information. Due to its small size and deep location within the brain, non-invasive mapping of the LGN and its microstructurally distinct subdivisions in humans is challenging. Using quantitative MRI methods that are sensitive to underlying microstructural tissue features, we show that a differentiation of the LGN and its microstructurally distinct subdivisions is feasible in humans non-invasively. These findings are important because they open up novel opportunities to assess the hitherto poorly understood complex role of the LGN in human perception and cognition, as well as the contribution of selective LGN subdivision impairments to various clinical conditions including developmental dyslexia, glaucoma and multiple sclerosis.

neuroscience↗